This is a request for an NIMH Research Scientist Development Award (K02). The broad objective of the research is to relate the clinical phenomenology of schizophrenia to brain structure and function. As an example of this approach, structural (MR) studies are outlined in the Research Plan of this application. Here, MR imaging techniques are proposed which represent an advance in imaging that has significantly broadened and enriched the neurological data base of schizophrenia. Accordingly, hypotheses regarding brain anomalies and their relationship to clinical phenomenology can now be more reliably and profitably explored. We plan to use these techniques to analyze MR scans (1.5-mm & 2-mm slices) from 75 chronic schizophrenics and 75 normal controls (matched for age, sex, handedness, & parental social class). Volumes will be determined for: 1) whole brain (gray matter, white matter & CSF); 2) temporal lobe (gray & white matter); 3) amygdala-hippocampal complex; 4) parahippocampal gyrus; 5) superior temporal gyrus (STG); 6) cingulate gyrus; and 7) prefrontal cortex (control region). An analysis of the gyral pattern in the cortical brain surface will also be completed. Additionally, we will extend and apply an MR brain atlas for the automatic identification of regions of interest (R01s). We predict that schizophrenics, compared to normals, will show volume reductions in temporal lobe limbic system structures (amygdala-hippocampal formation and parahippocampal gyrus), and in STG. We further predict that these abnormalities will be more pronounced on the left, and will be correlated with each other (thus indicating damage to an interconnected neural network) as well as correlated with positive but not negative symptoms. We expect cingulate gyrus volume to be correlated with tissue reductions in neuroanatomically linked regions in the temporal lobe. We also expect abnormalities to be visible in the 3D reconstructions of cortical gray matter where we predict that schizophrenics will show an abnormal temporal gyral pattern. We further predict that the brain atlas project will revolutionize what is now possible vis a vis the number of R01s that can be evaluated at any one time (i.e., minutes compared to months, currently, of labor intensive work). Plans for scientific enhancement include broadening and deepening knowledge in principles of MR scanning and MR imaging, and course work in advanced mathematics for the further understanding of the "warping" methods proposed for the MR atlas project. As part of career enhancement, the PI will also visit 5 prominent MR laboratories to increase understanding of different approaches to the investigation of brain abnormalities in schizophrenia. As part of the science education program, the PI will continue to serve as a mentor and to foster the research interests of young investigators. This funding is critical to enable the PI to devote full-time efforts to the rapidly developing research program begun during the tenure of the PI's RSDA (Level 1; 1988-1993). This program of research reflects the conviction that a fruitful marriage of clinical and cognitive skills with more biological methodologies is essential to the further understanding of the biology and psychology of schizophrenia, which is the overall goal of this proposal.